Tissue-specific gene expression of genome-wide significant loci associated with major depressive disorder subtypes

• Published in: Progress in neuro-psychopharmacology & biological psychiatry 2024-07, Vol.133, p.111019-111019, Article 111019
• Main Authors: Torii, Kaai, Ohi, Kazutaka, Fujikane, Daisuke, Takai, Kentaro, Kuramitsu, Ayumi, Muto, Yukimasa, Sugiyama, Shunsuke, Shioiri, Toshiki
• Format: Article
• Language: English
• Subjects: Brain; Depression; Female reproductive tissue; Gene expression; Subtype
• ISSN: 0278-5846; 1878-4216
• DOI: 10.1016/j.pnpbp.2024.111019

Major depressive disorder (MDD) is a clinically and genetically heterogeneous disorder. To reduce heterogeneity, large-scale genome-wide association studies have recently identified genome-wide significant loci associated with seven MDD subtypes. However, it was unclear in which tissues the genes near those loci are specifically expressed. We investigated whether genes related to specific MDD subtypes would be preferably expressed in a specific tissue. At 14 novel subtype-specific loci related to seven MDD subtypes—(1) non-atypical-like features MDD, (2) early-onset MDD, (3) recurrent MDD, (4) MDD with suicidal thoughts, (5) MDD without suicidal thoughts, (6) MDD with moderate impairment, and (7) postpartum depression, we investigated whether 22 genome-wide significant genetic variant-mapped genes were tissue-specifically expressed in brain, female reproductive, male specific, cardiovascular, gastrointestinal, or urinary tissues in the Genotype-Tissue Expression (GTEx) subjects (n ≤ 948). To confirm the tissue-specific expression in the GTEx, we used independent Human Protein Atlas (HPA) RNA-seq subjects (n ≤ 95). Of 22 genes, nine and five genes were tissue-specifically expressed in brain and female reproductive tissues, respectively (p